Sci. Aging Knowl. Environ., 23 October 2002
Vol. 2002, Issue 42, p. tg11

GENETICALLY ALTERED MICE

Liver-Specific IGF-1-Deficient Mice

http://sageke.sciencemag.org/cgi/content/full/sageke;2002/42/tg11


Mouse Liver-specific IGF-1-deficient (LID)
Genetic background ES cells: 129 SV; blastocysts: C57BL/6. Male chimeric mice were bred against female C57BL/6 mice. The F1 mice with germline transmission of the igf-1/flox locus were allowed to interbreed to generate homozygous igf-1/flox (F2) mice.
Gene changed insulin-like growth factor 1 (igf-1)
Type of change A targeted mutation using a neomycin cassette and loxP sites inserted to flank exon 4.
Nature of protein IGF-1 has 70 amino acid residues and three disulfide bridges. The liver is the major site of IGF-1 synthesis, although other organs contain igf-1 mRNA. IGF-1 is a regulator of somatic growth and cellular proliferation, because it is an inducer of (i) the phosphatidylinositol 3-kinase survival pathway (through activation of AKT1 and AKT2) and (ii) calcineurin-mediated signaling. These activities are inhibited by tumor necrosis factor.
Phenotype Although a complete igf-1-deficiency in mice is perinatal lethal (death occurs between embryonic day 18.5 and day 1 postnatal), when the igf-1 gene is deleted exclusively in the liver by use of the Cre/loxP system, the circulating levels of IGF-1 decrease dramatically, but the mice survive to adulthood and are phenotypically and behaviorally normal.
Corresponding human phenotype An igf-1 deficiency is believed to be the defect in the African pygmy [Online Mendelian Inheritance in Man (OMIM) entry number 265850] and has also been implicated in the Laron type of dwarfism (OMIM entry number 262500). It has also been suggested that the igf-1 gene may be the site of the mutation causing one form of hydrochondroplasia (OMIM entry number 146000). There is evidence to support the hypothesis that diminished concentrations of circulating IGF-1 play a role in age-related reduction of some cognitive functions.
Primary reference W. D. Naranjo, S. Yakar, M. Sanchez-Gomez, A. U. Perez, J. Setser, D. LeRoith, Protein calorie restriction affects nonhepatic IGF-1 production and the lymphoid system: studies using the liver-specific IGF-1 gene-deleted mouse model. Endocrinology 143, 2233-2241 (2002).
Additional references See below.
Source Not yet commercially available. Please contact authors of primary reference.
The Jackson Laboratory does have igf-1 transgenic mice, but they are phenotypically different from the LID mice. These alternative mouse strains include:
003078: FVB-TgN(WapIgf1)39Dlr
002500: C57BL/6J-TgN(wapIgf1)39Dlr
003258: Igf1 tm1Ts
003259: Igf1 tm2Ts
Other comments None
Other links OMIM entries for related human conditions:
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=265850
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=262500
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=146000
Related transgenic/knockout mice:
Ames Dwarf Mice:
http://sageke.sciencemag.org/cgi/content/full/sageke;2001/1/tg11
Growth Hormone Receptor Knockout (Laron) Mice:
http://sageke.sciencemag.org/cgi/content/full/sageke;2002/8/tg1
Little Mice:
http://sageke.sciencemag.org/cgi/content/full/sageke;2001/4/tg14
Snell Dwarf:
http://sageke.sciencemag.org/cgi/content/full/sageke;2001/3/tg13
SAGE KE's Genes/Interventions (database):
http://sageke.sciencemag.org/cgi/genedata/sagekeGdbGene;116
Keywords IGF-1, insulin, Cre/loxP
Prepared by Jennifer Fuller


October 23, 2002
  1. J. L. Liu, A. Grinberg, H. Westphal, B. Sauer, D. Accili, M. Karas, D. LeRoith, Insulin-like growth factor-1 affects perinatal lethality and postnatal development in a gene dosage-dependent manner: manipulation using the Cre/loxP system in transgenic mice. Mol. Endocrinol. 12, 1452-1462 (1998).[CrossRef][Medline]
  2. W. M. Naranjo, S. Yakar, M. Sanchez-Gomez, A. U. Perez, J. Setser, D. LeRoith, Protein calorie restriction affects nonhepatic IGF-1 production and the lymphoid system: studies using the liver-specific IGF-1 gene-deleted mouse model. Endocrinology 143, 2233-2241 (2002).[CrossRef][Medline]
  3. K. Sjogren, J. L. Liu, K. Blad, S. Skrtic, O. Vidal, V. Wallenius, D. LeRoith, J. Tornell, O. G. Isaksson, J. O. Jansson, C. Ohlsson, Liver-derived insulin-like growth factor 1 (IGF-1) is the principal source of IGF-1 in blood but is not required for postnatal body growth in mice. Proc. Natl. Acad. Sci. U.S.A. 96, 7088-7092 (1999).[Abstract/Free Full Text]
  4. S. Yakar, J. L. Liu, B. Stannard, A. Butler, D. Accili, B. Sauer, D. LeRoith, Normal growth and development in the absence of hepatic insulin-like growth factor 1. Proc. Natl. Acad. Sci. U.S.A. 96, 7324-7329 (1999).[Abstract/Free Full Text]
Citation: Liver-Specific IGF-1-Deficient Mice. Science's SAGE KE (23 October 2002), http://sageke.sciencemag.org/cgi/content/full/sageke;2002/42/tg11








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